Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO) and betaine—were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.

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Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

The fish gill is a multipurpose organ that, in addition to providing for aquatic gas exchange, plays dominant roles in osmotic and ionic regulation, acid-base regulation, and excretion of nitrogenous wastes Thus, despite the fact that all fish groups have functional kidneys, the gill epithelium is the site of many processes that are mediated by renal epithelia in terrestrial vertebrates Indeed, many of the pathways that mediate these processes in mammalian renal epithelial are expressed in the gill, and many of the extrinsic and intrinsic modulators of these processes are also found in fish endocrine tissues and the gill itself The basic patterns of gill physiology were outlined over a half century ago, but modern immunological and molecular techniques are bringing new insights into this complicated system Nevertheless, substantial questions about the evolution of these mechanisms and control remain

https://people.clas.ufl.edu/devans/files/PRVGill.pdf

The Multifunctional Fish Gill: Dominant Site of Gas Exchange, Osmoregulation, Acid-Base Regulation, and Excretion of Nitrogenous Waste

Lipids and their constituent fatty acids are, along with proteins, the major organic constituents of fish, and they play major roles as sources of metabolic energy for growth including reproduction and movement, including migration. Furthermore, the fatty acids of fish lipids are rich in ω3 long chain, highly unsaturated fatty acids (n-3 HUFA) that have particularly important roles in animal nutrition, including fish and human nutrition, reflecting their roles in critical physiological processes. Indeed, fish are the most important food source of these vital nutrients for man. Thus, the longstanding interest in fish lipids stems from their abundance and their uniqueness. This review attempts to summarize our present state of knowledge of various aspects of the basic biochemistry, metabolism, and functions of fatty acids, and the lipids they constitute part of, in fish, seeking where possible to relate that understanding as much to fish in their natural environment as to farmed fish. In doing so, it highli...

/pdf/metabolism-and-functions-of-lipids-and-fatty-acids-in-566zpmr4m0.pdf

Metabolism and Functions of Lipids and Fatty Acids in Teleost Fish

A positive temperature coefficient is the term which has been used to indicate that an increase in solubility occurs as the temperature is raised, whereas a negative coefficient indicates a decrease in solubility with rise in temperature.

Effect of Temperature

counteract perturbations by urea (eg in elasmobranchs and mammalian kidney), inorganic ions, and hydrostatic pressure in deep-sea animals Trehalose and proline in overwintering insects stabilize membranes at subzero temperatures Trehalose in insects and yeast, and anionic polyols in microorganisms around hydrothermal vents, can protect proteins from denaturation by high temperatures Third, stabilizing solutes appear to be used in nature only to counteract perturbants of macromolecules, perhaps because stabilization is detrimental in the absence of perturbation Some of these solutes have applications in biotechnology, agriculture and medicine, including in vitro rescue of the misfolded protein of cystic fibrosis However, caution is warranted if high levels cause overstabilization of proteins

/pdf/organic-osmolytes-as-compatible-metabolic-and-counteracting-3nlnu54927.pdf

Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses

Energy metabolism and contractility in ectothermic vertebrate hearts: hypoxia, acidosis, and low temperature

Hearts from 16 species of fishes, including representatives of cyclostomes, elasmobranchs, and teleosts, were examined. As a biochemical index of maximal ATP demand, ATPase activity of crude homogenates of ventricular tissue was measured under conditions which optimize activity of myofibrils and inhibit nonphysiological mitochondrial F₁-ATPase by inclusion of oligomycin in the assay medium. The activities of nine additional enzymes from pathways of energy metabolism and concentration of myoglobin-an intracellular protein involved in storage and diffusion of oxygen-were measured. Of all possible pairwise regressions between these biochemical markers, only the relationships among ATPase, carnitine palmitoyltransferase (CPT), and hexokinase (HK) and between HK and phosphofructokinase (PFK) were significant. The inability of elasmobranch myocardium to catabolize fatty acid is confirmed. ATP yields calculated from HK and CPT and corrected to reflect physiological conditions of the tissue suggest that catabolis...

Biochemical Correlations of Power Development and Metabolic Fuel Preferenda in Fish Hearts

This chapter describes the biochemical events involved in the transition from a resting to an actively swimming condition. The chapter deals with metabolism in myotomal muscle, but there are other organs, integrally important for the maintenance of homeostasis, that may be extremely expensive to operate during sustained swimming. For instance, the cost of osmoregulation, in freshwater, for actively swimming rainbow trout ( Salmo gairdneri ), may be as high as 30% of the total metabolism of the fish. Much of this energy expenditure must be borne by the gills. The cost of maintaining the cardiac pump may also be quite substantial. In fact, at high oxygen consumption rates, this may approach 15% of the total metabolism of the animal. Thus, the myotomal muscle per se may account for only about 50% of the total energy output. In light of this, it is somewhat surprising that tissues other than skeletal muscle are rarely studied by fish physiologists interested in metabolic alterations during swimming. The chapter describes the control of metabolism in these support tissues and skeletal muscle; however, the understanding of metabolism in fish tissues is at best fragmentary. Hence, where appropriate, the better-studied mammalian systems are called upon to complement and supplement the discussion.

8 - Metabolism in Fish During Exercise

Common carp (Cyprinus carpio L.), 1 kg body weight, were acclimated for 1-2 months to water temperatures of either 7-8 degrees C (cold-acclimated group) or 23-24 degrees C (warm-acclimated group). Single fast fibres and small bundles of slow fibres were isolated from the myotomal muscles and chemically skinned. Force-velocity (P-V) characteristics were determined at 7 degrees C and 23 degrees C. The contractile properties of carp muscle fibres are dependent on acclimation temperature. In the warm-acclimated group maximum isometric tensions (P0, kN m-2) are 47 +/- 6 and 64 +/- 5 for slow muscle fibres and 76 +/- 10 and 209 +/- 21 for fast muscle fibres at 7 degrees C and 23 degrees C, respectively. Maximum contraction velocities (Vmax, muscle lengths-1), are 0.4 +/- 0.05 and 1.5 +/- 0.1 at 7 degrees C (slow fibres) and 0.6 +/- 0.04 and 1.9 +/- 0.4 at 23 degrees C (fast fibres). All values represent mean +/- S.E. P0 and Vmax at 7 degrees C are around 1.5-2.0 times higher for slow and fast muscle fibres isolated from the cold-acclimated group. Fibres from 7 degrees C-acclimated carp fail to relax completely following maximal activations at 23 degrees C. The resulting Ca-insensitive force component (50-70% P0) is associated with the development of abnormal crossbridge linkages and very slow contraction velocities. Activities of enzymes associated with energy metabolism were determined at a common temperature of 15 degrees C. Marker enzymes of the electron transport system (cytochrome oxidase), citric acid cycle (citrate synthase), fatty acid metabolism (carnitine palmitoyl transferase, beta-hydroxyacyl CoA dehydrogenase) and aerobic glucose utilization (hexokinase) have 30-60% higher activities in slow muscle from cold-acclimated than from warm-acclimated fish. Activities of cytochrome oxidase and citrate synthase in fast muscle are also elevated following acclimation to low temperature. It is concluded that thermal compensation of mechanical power output by carp skeletal muscle is matched by a concomitant increase in the potential to supply aerobically-generated ATP at low temperatures.

Force-velocity characteristics and metabolism of carp muscle fibres following temperature acclimation

In late summer, semipalmated sandpipers (Calidris pusilla) migrate nonstop from eastern Canada to wintering sites on the northwest coast of South America. Before their transoceanic flight, the birds feed intensively for about 15 days during which time lipids are stored. The fat-free dry mass of the pectoralis muscle increases during the fattening period, probably increasing the maximal power output of the muscle. Plasma free fatty acids and triglycerides, pectoralis muscle lipid content, and the activity of carnitine oleoyl coenzyme A transferase are higher in heavy (fat) than in light (lean) birds. These alterations imply an enhanced capacity to utilize fatty acids as a metabolic fuel during migration. Total pectoralis muscle glycogen levels and the activity of pyruvate kinase increase, suggesting a higher capacity for glycogenolysis, which may be important during intense levels of energy demand. Heart size and protein content per gram of tissue increase in association with an increase in body mass. Howe...

William R. Driedzic

Papers

Energy metabolism and contractility in ectothermic vertebrate hearts: hypoxia, acidosis, and low temperature

Biochemical Correlations of Power Development and Metabolic Fuel Preferenda in Fish Hearts

8 - Metabolism in Fish During Exercise

Force-velocity characteristics and metabolism of carp muscle fibres following temperature acclimation

Adaptations in pectoralis muscle, heart mass, and energy metabolism during premigratory fattening in semipalmated sandpipers (Calidris pusilla)